Sarah Chiang

Memorial Sloan-Kettering Cancer Center, New York City, New York, United States

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Publications (10)32.49 Total impact

  • Sarah Chiang, Robert A. Soslow
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    ABSTRACT: Diagnostic difficulty in the morphologic assessment of endometrial carcinomas may arise in pathology practice. Challenges in tumor classification exist especially in the setting of high-grade carcinomas. These include FIGO grade 3 endometrioid, serous, clear cell, and undifferentiated carcinomas, in addition to carcinomas of mixed cell type and those exhibiting ambiguous morphologic features. This comprehensive review details key morphologic and immunophenotypic features of prototypic endometrial carcinomas, including a description of both well-established and novel immunohistochemical markers in the evaluation of these tumors. It also provides recommendations regarding prudent use of these ancillary techniques in distinguishing between various histologic subtypes of endometrial carcinoma that frequently result in persistent diagnostic problems.
    Seminars in Diagnostic Pathology 01/2014; · 1.62 Impact Factor
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    ABSTRACT: Endometrial stromal sarcomas with the YWHAE-NUTM2A/B genetic fusion characteristically contain high-grade round to epithelioid cell component that is strongly and diffusely cyclin D1-positive and it may or may not show an associated low-grade fibroblastic/myxoid cell component. They are clinically more aggressive than endometrial stromal sarcomas with the JAZF1-SUZ12 genetic fusion and frequently demonstrate extrauterine extension at initial clinical presentation. In this setting, the tumor may be misdiagnosed as gastrointestinal stromal tumor. This study examines the expression of KIT and ANO1 in 14 YWHAE-NUTM2A/B tumors by immunohistochemistry. Staining localization was determined as membranous and/or cytoplasmic, and the staining intensity was assessed (negative, weak, moderate and strong). Of the 14 tumors, 6 contained only a high-grade round cell component, 2 only a low-grade fibroblastic component and 6 had both components in the slides evaluated. The high-grade round cell component displayed moderate to strong membranous/cytoplasmic KIT staining in all tumors (12 of 12). The low-grade fibroblastic cell component showed only weak cytoplasmic KIT staining in 3 of 8 tumors. In contrast, ANO1 was negative in all 14 neoplasms, irrespective of the component evaluated. Sanger sequencing analysis (exons 9, 11, 13 and 17) and Ampliseq Cancer Panel mutation screen (Ion Torrent) demonstrated no KIT mutations in three KIT-positive YWHAE-NUTM2A/B tumors. This study shows that the high-grade round cell component of YWHAE-NUTM2A/B endometrial stromal sarcoma consistently expresses KIT but lacks KIT hotspot mutations. KIT expression may represent a potential diagnostic pitfall in the evaluation of YWHAE-NUTM2A/B endometrial stromal sarcoma presenting with pelvic/abdominal mass, particularly in situations where its uterine origin is not definitive, and thus a panel of antibodies that includes ANO1 and cyclin D1 is necessary.Modern Pathology advance online publication, 1 November 2013; doi:10.1038/modpathol.2013.199.
    Modern Pathology 11/2013; · 5.25 Impact Factor
  • Sarah Chiang, Esther Oliva
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    ABSTRACT: Smooth muscle and endometrial stromal tumours represent the two most common uterine mesenchymal neoplasms that may present diagnostic dilemmas for the practising surgical pathologist. Recent changes in morphological and staging criteria, as well as the discovery of new immunohistochemical markers, have improved the diagnosis and classification of these tumours. We highlight the difficulty in distinguishing tumour cell necrosis from infarct-type necrosis and the limited utility of p16 immunohistochemical expression in the diagnosis of leiomyosarcoma. We also discuss the controversial use of mitotic activity and necrosis as prognostic factors in endometrial stromal sarcomas. Emerging genetic information has also greatly expanded our understanding of 'sarcomagenesis' in both tumour types and may provide insight into potential therapeutic targets for the treatment of leiomyosarcoma and endometrial stromal sarcomas, harboring MED12 (mediator complex subunit 12) mutations and recurrent gene rearrangements, respectively. In this review, we discuss the core updates in the diagnosis and classification of uterine leiomyosarcomas and endometrial stromal sarcomas, highlighting new and important molecular genetic findings that may drive pathogenesis.
    Histopathology 01/2013; 62(1):124-37. · 2.86 Impact Factor
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    ABSTRACT: Endometrial stromal sarcoma (ESS) characterized by YWHAE-FAM22 genetic fusion is histologically higher grade and clinically more aggressive than ESS with JAZF1-SUZ12 or equivalent genetic rearrangements, hence it is clinically important to recognize this subset of ESS. To identify diagnostic immunomarkers for this biologically defined ESS subset, we compared gene expression profiles between YWHAE-FAM22 ESS and JAZF1-rearranged ESS. These studies showed consistent upregulation of cyclin D1 in YWHAE-FAM22 ESS compared with JAZF1-SUZ12 ESS. Immunohistochemically, the high-grade round cell component of all 12 YWHAE-FAM22 ESS demonstrated diffuse (≥70%) moderate to strong nuclear cyclin D1 staining, and this diffuse positivity was not seen in 34 ESSs with JAZF1 and equivalent genetic rearrangements or in 21 low-grade ESS with no demonstrable genetic rearrangements. In a series of 243 non-ESS pure uterine mesenchymal and mixed epithelial-mesenchymal tumors, only 2 of 8 undifferentiated endometrial sarcomas with nuclear uniformity and 1 of 80 uterine leiomyosarcomas demonstrate diffuse cyclin D1 immunoreactivity. Both cyclin D1-positive undifferentiated endometrial sarcomas showed diffuse strong CD10 staining, which is consistently absent in the high-grade round cell component of YWHAE-FAM22 ESS. The low-grade spindle cell component of YWHAE-FAM22 ESS showed a spatially heterogenous cyclin D1 staining pattern that was weaker and less diffuse overall. Our findings indicate that cyclin D1 is a sensitive and specific diagnostic immunomarker for YWHAE-FAM22 ESS. When evaluating high-grade uterine sarcomas, cyclin D1 can be included in the immunohistochemical panel as an indicator of YWHAE-FAM22 ESS.
    The American journal of surgical pathology 10/2012; 36(10):1562-1570. · 4.06 Impact Factor
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    ABSTRACT: Potential sources of error in surgical pathology include specimen misidentification, unidentified tissue, and tissue contamination of paraffin blocks and slides. Current molecular approaches to characterize unidentified or misidentified tissue include fluorescence in situ hybridization identification of sex chromosomes (XY FISH) and microsatellite analysis. Polymorphic deletion probe (PDP) FISH, a novel FISH assay based on copy number variants, can distinguish between cells and tissues from 2 individuals in situ, independent of gender. Using a panel of 3 PDPs, we compared the genotypes of potential tissue contaminants (n=19) and unidentified tissues (n=6) with patient tissues to determine the utility of PDP FISH in resolving specimen identity. XY FISH was added to increase the informative potential of the assay, and microsatellite analysis was used as a gold standard to confirm PDP FISH results. PDP FISH distinguished between putative contaminants and patient tissues in 13 of 14 cases and indicated a high likelihood of 2 tissues originating from the same source in 11 of 11 cases. The assay has a sensitivity and specificity of 86% [6/7, exact 95% confidence interval (CI): 42%, 97%] and 100% (9/9, exact 1-sided 97.5% CI: 68%, 100%), respectively, and a positive predictive value and negative predictive value of 100% (6/6, exact 1-sided 97.5% CI: 54%, 100%) and 90% (9/10, exact 95% CI: 55%, 98%), respectively. PDP FISH is an accurate and practical molecular assay for the genetic characterization of potential tissue contaminants and unidentified tissues, especially in the setting of small sample size, and permits concomitant assessment of morphology.
    The American journal of surgical pathology 10/2012; 36(10):1464-71. · 4.06 Impact Factor
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    ABSTRACT: Endometrial stromal sarcoma (ESS) is a genetically heterogenous group of uterine sarcomas, of which almost half are associated with JAZF1 rearrangement. We recently identified a novel genetic fusion between YWHAE and FAM22A/B in ESS harboring t(10;17)(q22;p13) and herein describe the clinicopathologic features of 13 YWHAE-FAM22 ESS cases (11 primary and 3 metastatic) and compare them with 20 ESS cases with JAZF1 rearrangement. Ten of 11 primary uterine tumors contained morphologically high-grade areas composed of round cells arranged in nests with a delicate stromal capillary network. The tumor cells showed large nuclei with irregular nuclear contours and significant mitotic activity (>10 mitoses/10 HPF) in addition to focal tumor necrosis, in contrast to JAZF1 ESS, which lacked a nested growth pattern, were composed of cells with small round/oval nuclei, and typically had <5 MF/10 HPF. In 7 of the 11 uterine tumors, there was an additional cytologically bland and mitotically weakly active spindle cell component with a fibrous/fibromyxoid stroma (ESS, fibromyxoid variant). Two metastatic tumors (pulmonary) also contained round cell and spindle cell components, whereas 1 metastasis (vaginal) was composed solely of the spindle cell component. In both primary and metastatic tumors, the spindle cells were diffusely positive for estrogen and progesterone receptors and CD10, in contrast to the round cell areas, which were negative. Clinically, 10 of 12 patients with YWHAE-FAM22 ESS presented with FIGO stages II to III disease, in contrast to only 4 of 16 patients with JAZF1 ESS presenting with stages II to III disease (P<0.05). Tumors with YWHAE-FAM22 rearrangements constitute a distinct group of ESS, which is associated with high-grade morphology and aggressive clinical behavior compared to JAZF1 ESS. Thus, their distinction from typical JAZF1 ESS is important for prognostic and therapeutic purposes.
    The American journal of surgical pathology 03/2012; 36(5):641-53. · 4.06 Impact Factor
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    ABSTRACT: Translocations resulting in gene fusion are characteristic of endometrial stromal tumors (ESTs). Rearrangements of JAZF1, SUZ12, PHF1, and EPC1 have been reported in endometrial stromal nodules (ESNs), endometrial stromal sarcomas (ESSs), and rarely in undifferentiated endometrial sarcomas (UESs). Detection of JAZF1, SUZ12, EPC1, and PHF1 rearrangement by fluorescence in situ hybridization was performed on tissue microarrays consisting of 94 ESTs of classic and variant morphology (20 ESNs, 43 primary uterine ESSs, 15 metastatic uterine ESSs, 4 primary extrauterine ESSs, 7 primary uterine UESs, and 5 unclassified ESTs), 16 Müllerian adenosarcomas, 2 malignant mixed Müllerian tumors, 2 uterine tumors resembling ovarian sex-cord tumors, 2 highly cellular leiomyomas, 1 leiomyosarcoma, and 7 polypoid endometriosis. Rearrangements were detected in 42 of 78 (54%) uterine ESTs, with JAZF1-SUZ12 fusion found in 50% of ESNs and in 33% of ESSs and JAZF1-PHF1 and EPC1-PHF1 fusions found in 1% and <1% of ESSs, respectively. PHF1 and JAZF1 were rearranged with unknown partners in 8 uterine ESTs. JAZF1-SUZ12 fusion, EPC1-PHF1 fusion, and PHF1 rearrangement were found in 3 extrauterine ESSs, whereas no rearrangements were observed in UESs or in any other non-EST studied. Our data confirm that gene rearrangements are present in more than 50% of uterine ESTs, with JAZF1-SUZ12 fusion being the most common, followed by rare EPC1-PHF1 and JAZF1-PHF1 fusions. The presence of identical gene rearrangements in both uterine and extrauterine ESTs suggests a similar pathogenesis. The presence of detectable gene rearrangements in uterine ESS may predict better patient outcome.
    The American journal of surgical pathology 09/2011; 35(9):1364-72. · 4.06 Impact Factor
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    ABSTRACT: Because products of conception often contain maternal and villous tissues, the determination of maternal and villous genotypes based on genetic polymorphisms can help discern maternal and paternal chromosomal contribution and aid in the diagnosis of hydatidiform moles. Polymorphic deletion probe (PDP) fluorescence in situ hybridization (FISH) probes based on copy number variants are highly polymorphic and allow in situ determination of genetic identity. By using three informative PDPs on chromosomes 2p, 4q, and 8p, we compared maternal with villous genotypes and determined the ploidy of villous tissue. PDP FISH was performed on 13 complete moles, 13 partial moles, 13 nonmolar abortions, and an equivocal hydropic abortion. PDP FISH permitted definitive diagnosis of complete moles in five of 13 cases for which maternal and villous genotypes were mutually exclusive. A complete mole was highly suspected when all three PDP loci showed homozygous villous genotypes. The diagnosis of a complete mole by PDP FISH yielded a theoretical test sensitivity of 87.5%, specificity of 91.8%, an observed test sensitivity of 100%, and specificity of 92.3%. Triploidy was observed in all partial moles, in which diandric triploidy was confirmed in six cases. In the equivocal hydropic abortion, PDP FISH combined with p57 immunofluorescence revealed placental androgenetic/biparental mosaicism. PDP FISH can be used in clinical practice and research studies to subclassify hydatidiform moles and evaluate unusual products of conception.
    The Journal of molecular diagnostics: JMD 07/2011; 13(4):406-15. · 3.48 Impact Factor
  • Sarah Chiang, Esther Oliva
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    ABSTRACT: Endometrial stromal tumors (ESTs) are rare uterine mesenchymal tumors, comprising <10% of all uterine mesenchymal neoplasms. The latest World Health Organization classification divides endometrial stromal tumors into 3 categories based on morphologic features: endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma, and undifferentiated endometrial sarcoma. Specific cytogenetic aberrations and molecular genetic alterations have recently been identified in endometrial stromal tumors, providing insights into their molecular biology, potential diagnostic markers, and possible therapeutic targets. Currently, recurrent chromosomal rearrangements resulting in gene fusion play a substantive role in the pathogenesis of endometrial stromal nodules, endometrial stromal sarcomas, and a small subset of undifferentiated endometrial sarcomas. Loss of heterozygosity of tumor suppressor genes and deregulation of the Wnt signaling pathway have also been implicated in EST tumorigenesis. In this review, we summarize the recent advances in the molecular pathology of endometrial stromal tumors.
    Human pathology 03/2011; 42(5):609-17. · 3.03 Impact Factor
  • Source
    Sarah Chiang, Esther Oliva
    Human Pathology - HUM PATHOL. 01/2011; 42(10):1580-1580.

Publication Stats

70 Citations
32.49 Total Impact Points

Institutions

  • 2014
    • Memorial Sloan-Kettering Cancer Center
      • Department of Pathology
      New York City, New York, United States
  • 2013
    • Royal Alexandra Hospital
      Edmonton, Alberta, Canada
  • 2011–2013
    • Massachusetts General Hospital
      • Department of Pathology
      Boston, MA, United States
    • Harvard Medical School
      • Department of Pathology
      Boston, Massachusetts, United States